(1) Field of the Invention
The present invention generally relates to compounds having pharmacological activity which are useful as pharmaceutical agents and, more particularly, as analgesic agents for the treatment of pain, and as agents for the treatment of prostaglandin-E.sub.2 mediated diseases, to pharmaceutical compositions containing one or more of these compounds, and to methods of treatment employing these compounds. More particularly, the present invention concerns substituted dibenzoxazepine compounds, pharmaceutical compositions containing one or more of these compounds in combination with a pharmaceutically-acceptable carrier, and medical methods of treating pain and prostaglandin-E.sub.2 mediated diseases employing these compounds.
Analgesic compounds are agents which alleviate pain without causing a loss of consciousness and, thus, which are useful for treating pain and, often, for reducing inflammation.
The major classes of analgesic compounds include narcotic analgesics, or opiates, compounds which alleviate pain and induce sleep, and analgesicantipyretic compounds, compounds which alleviate pain and reduce fever, such as salicylates.
Although the efficacy of opiates in relieving pain is well established, the associated addiction liability of opiates is a distinct disadvantage of these compounds.
While silicylate and salicylate-like agents (nonsteroidal antiinflammatory agents or NSAIDS) are also efficacious in relieving pain, they often exhibit undesirable side effects, such as gastrointestinal irritation, as with aspirin, allergic response, as with aspirin, and/or liver toxicity with extended use, as with acetaminophen.
The compounds of the present invention are neither opiates nor salicylates, and represent another class of compounds which are useful as analgesic agents.
(2) Description of the Related Art
U.S. Pat. No. 3,624,104 discloses aralkanoyl derivatives of dibenzoxazepine-N-carboxylic acid hydrazide compounds.
U.S. Pat. No. 3,917,649 discloses dibenzoxazepine N-carboxylic acid hydrazine compounds.
U.S. Pat. No. 4,290,953 discloses dibenz b,f! 1,4!oxazepine derivatives.
U.S. Pat. No. 4,045,442 disclose 1-(substituted amino)alkanoyl-2-(dibenzoxazepine-10-carbonyl)hydrazine compounds.
U.S. Pat. No. 4,379,150 discloses dibenz b,f! 1,4!oxazepine derivatives which may have a heterocyclic ring in the side chain at the 10-position of the compounds.
U.S. Pat. No. 4,681,939 discloses 8-chlorodibenz b,f! 1,4!-oxazepine-10(11H)-carboxylic acid, 2- (substituted phenylsulfinyl)alkanoyl!hydrazides and 8-chlorodibenz b,f! 1,4!oxazepine(11H)-carboxylic acid, 2- (substituted phenylsulfonyl)alkanoyl!hydrazides.
U.S. Pat. No. 4,704,386 discloses 8-chlorodibenz b,f! 1,4!-oxazepine-10(11H)-carboxylic acid, 2- (substituted phenylsulfinyl)alkanoyl!hydrazides and 8-chlorodibenz b,f! 1,4!oxazepine(11H)-carboxylic acid, 2- (substituted phenylsulfonyl)alkanoyl!hydrazides.
U.K. Pat. No. 1,522,003 discloses 1-acyl-2-(8-chloro-10,11-dihydrodibenz b,f! 1,4!oxazepine-10-carbonyl)hydr azines.
U.K. Pat. No. 1,331,892 discloses dibenzoxazepine N-carboxylic acid hydrazides.
U.S. Pat. No. 4,888,335 discloses 3-alkoxy-2-aminopropyl heterocyclic amines.
U.S. Pat. No. 4,360,525 discloses 10-(4-piperidinyl)-10,11-dihydro-dibenz- b,f! 1,4!oxazepines, -dibenzo b,f! 1,4!thiazepines and -5H-dibenzo b,e! 1,4!diazepines.
European Patent Application Publication No. 0 480 641 A1 discloses tricyclic heterocycles which may contain unsubstituted or substituted phenylene in the side chain at the 10-position of the compounds.
European Patent Application Publication No. 0 534 667 A1 discloses substituted tricyclic heterocycles which contain a heteroaryl group in the side chain at the 10-position of the compounds.
European Patent Application Publication No. 0 218 077 discloses 8-chlorodibenz b,f! 1,4!oxazepine-10(11H)-carboxylic acid, 2- (substituted phenylsulfinyl)alkanoyl!hydrazide compounds and 8chlorodibenz b,f! 1,4!oxazepine-10(11H)-carboxylic acid, 2- (substituted phenylsulfonyl)alkanoyl!hydrazide compounds, and intermediates used in the preparation of these compounds.
J. H. Sanner, "Dibenzoxazepine Hydrazides as Prostaglandin Antagonists," Intra-Science Chem Rept., 6(1), 1-9 (1972), describes experiments performed with two dibenzoxazepine derivatives designated SC-18637 and SC-19220, and found that SC-18637 and SC-19220 inhibit the stimulant actions of prostaglandins on isolated smooth muscle preparations.
Each of the documents described hereinabove discloses compounds which are structurally different from the compounds of the present invention. The compounds of the present invention are structurally distinct from that which has been described in the art.